Genetic Variant NM_144572.2:c.*1527C>G (chr15-77996633-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144572.2(TBC1D2B):c.*1527C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,238 control chromosomes in the GnomAD database, including 3,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3447 hom., cov: 34)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

TBC1D2B
NM_144572.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.844

Publications

14 publications found

Variant links:

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D2B Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures and gingival overgrowth
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

TBC1D2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D2B	NM_144572.2 link	c.*1527C>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000300584.8	NP_653173.1	Q9UPU7-1B2RTQ2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D2B	ENST00000300584.8 link	c.*1527C>G	3_prime_UTR_variant	Exon 13 of 13	5	NM_144572.2	ENSP00000300584.3	Q9UPU7-1
TBC1D2B	ENST00000409931.7 link	c.*1622C>G	3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000387165.3	Q9UPU7-2
TBC1D2B	ENST00000418039.2 link	n.2749C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
TBC1D2B	ENST00000465531.1 link	c.64+4986C>G	intron_variant	Intron 1 of 1	4		ENSP00000453114.1	H0YL97

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30275

AN:

152112

Hom.:

3444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.199

AC:

30286

AN:

152230

Hom.:

3447

Cov.:

AF XY:

0.203

AC XY:

15112

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0711

AC:

2954

AN:

41548

American (AMR)

AF:

0.191

AC:

2924

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

538

AN:

3472

East Asian (EAS)

AF:

0.350

AC:

1814

AN:

5184

South Asian (SAS)

AF:

0.227

AC:

1095

AN:

4824

European-Finnish (FIN)

AF:

0.281

AC:

2970

AN:

10578

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17268

AN:

68012

Other (OTH)

AF:

0.190

AC:

400

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1274

2548

3823

5097

6371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.215

Hom.:

503

Bravo

AF:

0.187

Asia WGS

AF:

0.264

AC:

922

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.6

(source)

DANN

Benign

0.44

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over